Divarasib vs Other Treatments for Lung Cancer

(Krascendo 1 Trial)

Recruiting at 265 trial locations

Overseen By Reference Study ID Number: BO45217 https://forpatients.roche.com/

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 3

Recruiting

Sponsor: Hoffmann-La Roche

Must not be taking: KRAS inhibitors

Disqualifiers: CNS metastases, Leptomeningeal disease, others

No Placebo Group

Pivotal Trial (Near Approval)

Prior Safety Data

Breakthrough Therapy

Trial Summary

What is the purpose of this trial?

The purpose of this study is to assess the safety and efficacy of divarasib compared to locally approved KRAS G12C inhibitors (sotorasib or adagrasib) in participants with KRAS G12C-positive (KRAS G12C +) advanced or metastatic non-small cell lung cancer (NSCLC).

Do I need to stop my current medications to join the trial?

The trial information does not specify if you need to stop taking your current medications. It's best to discuss this with the trial team or your doctor.

What data supports the effectiveness of the drug Divarasib for lung cancer?

Research shows that the drug adagrasib, also known as MRTX849, is effective in treating non-small cell lung cancer with a specific mutation (KRAS G12C), with studies reporting good tolerance and significant effectiveness. Additionally, when combined with another drug, pembrolizumab, it showed promising response rates in newly diagnosed patients. ^{1 2 3 4 5}

Is Divarasib (also known as Adagrasib, Sotorasib, etc.) generally safe for humans?

Research shows that Divarasib (also known as Adagrasib) and Sotorasib are generally well tolerated in humans, with common side effects including diarrhea, muscle pain, nausea, fatigue, liver issues, and cough. These drugs have been tested in people with lung cancer and other solid tumors, showing they are mostly safe with manageable side effects. ^{1 2 4 5 6}

How is the drug Divarasib different from other treatments for lung cancer?

Divarasib, like adagrasib and sotorasib, targets the KRASG12C mutation in non-small cell lung cancer, which is a specific genetic change in cancer cells. These drugs are unique because they specifically inhibit this mutation, offering a targeted approach for patients with this genetic profile, unlike traditional chemotherapy that affects all rapidly dividing cells. ^{2 5 7 8 9}

Research Team

Clinical Trials

Principal Investigator

Hoffmann-La Roche

Eligibility Criteria

This trial is for people with advanced or metastatic non-small cell lung cancer (NSCLC) that has a specific mutation known as KRAS G12C. Participants should have previously been treated for their condition.

Inclusion Criteria

My cancer has a KRAS G12C mutation.

My cancer has worsened despite 1-3 treatments.

Measurable disease according to Response Evaluation Criteria in Solid Tumors (RECIST) v1.1

Exclusion Criteria

Known hypersensitivity to any of the components of divarasib, sotorasib, or adagrasib

I do not have conditions that affect how my body absorbs food.

I have pain from my cancer that isn't relieved by treatment.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive divarasib or a KRAS G12C inhibitor (sotorasib or adagrasib) orally

Up to approximately 4 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

Treatment Details

Interventions

• Adagrasib (Other)
• Divarasib (Other)
• Sotorasib (Other)

Trial Overview The study is testing the effectiveness and safety of a new drug called Divarasib compared to already approved drugs, Sotorasib or Adagrasib, in patients with the KRAS G12C mutation in NSCLC.

Participant Groups

Group I: Divarasib Experimental Treatment 1 Intervention

Participants will receive divarasib orally, once daily (QD).

Group II: KRAS G12C inhibitor Active Control 2 Interventions

Participants will receive Sotorasib orally QD or adagrasib orally twice a day (BID)

Who Is Running the Clinical Trial?

Hoffmann-La Roche

Lead Sponsor

Trials

2,482

Recruited

1,107,000+

Headquarters

Basel, Switzerland

Known For

Precision medicine

Top Products

Avastin, Herceptin, Rituxan, Accu-Chek

Dr. Levi Garraway

Hoffmann-La Roche

Chief Medical Officer since 2019

MD from the University of Basel

Dr. Thomas Schinecker

Hoffmann-La Roche

Chief Executive Officer since 2023

PhD in Molecular Biology from New York University

Chugai Pharmaceutical

Industry Sponsor

Trials

105

Recruited

25,000+

Dr. Osamu Okuda

Chugai Pharmaceutical

Chief Executive Officer since 2020

MD from Kyoto University

Dr. Mariko Y. Momoi

Chugai Pharmaceutical

Chief Medical Officer

MD from Jichi Medical University

Findings from Research

Sotorasib and adagrasib, both KRAS G12C-targeting agents, have shown promising efficacy in treating non-small cell lung cancer (NSCLC), with sotorasib achieving an overall response rate of 41% and a progression-free survival of 6.3 months, while adagrasib had an overall response rate of 42.9% and a progression-free survival of 6.5 months.

Both drugs have received accelerated FDA approval and are now recommended as second-line treatment options for patients with KRAS G12C-mutated NSCLC, although they come with common side effects like diarrhea and fatigue, highlighting the need for further studies to refine their use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Targeted Therapies for Previously "Undruggable" KRAS-Mutated Non-Small Cell Lung Cancer: A Review of Sotorasib and Adagrasib. Mausey, N., Halford, Z.[2023]

The KRYSTAL-1 study found that adagrasib (MRTX849), a KRASG12c inhibitor, is generally well tolerated by patients with non-small cell lung cancer, indicating a favorable safety profile.

Adagrasib demonstrated significant efficacy in treating non-small cell lung cancer with the KRASG12c mutation, and it also showed some activity in colorectal cancer and other solid tumors, although to a lesser extent.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Another KRAS Inhibitor Holds Its Own. [2021]

Sotorasib is the first commercially available KRASG12C inhibitor, showing promise in improving outcomes for patients with KRASG12C-mutated non-small cell lung cancer (NSCLC), which is prevalent among smokers.

Despite its potential, there are ongoing questions about sotorasib's effectiveness in the brain, optimal dosing, and how it compares to standard treatments, highlighting the need for further research on resistance mechanisms and combination therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. Strohbehn, GW., Sankar, K., Qin, A., et al.[2022]

In the phase I/II CodeBreaK100 trial, the KRASG12C inhibitor sotorasib demonstrated a 21.1% objective response rate in patients with pancreatic ductal adenocarcinoma who had previously undergone at least one therapy.

Additionally, sotorasib achieved an impressive 84.2% disease control rate, indicating its potential effectiveness in managing this challenging cancer type.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib Tackles KRASG12C-Mutated Pancreatic Cancer. [2022]

Adagrasib combined with pembrolizumab shows promising efficacy for patients with newly diagnosed non-small cell lung cancer with a KRASG12C mutation, achieving overall response rates of 49% and 57% in two separate trials.

This drug combination demonstrated a favorable safety profile, exhibiting lower liver toxicity compared to other combinations of checkpoint inhibitors and targeted therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

Sotorasib (Lumakras) received accelerated FDA approval for treating advanced non-small cell lung cancer (NSCLC) with a KRAS G12C mutation, showing an overall response rate of 36% in a study of 124 patients.

The median duration of response to sotorasib was 10 months, with common side effects including diarrhea, musculoskeletal pain, and nausea, highlighting its efficacy and safety profile as a targeted therapy for this specific cancer mutation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC. Nakajima, EC., Drezner, N., Li, X., et al.[2022]

In the phase II KRYSTAL-1 trial, the KRASG12C inhibitor adagrasib demonstrated a 43% overall response rate and an 80% disease control rate in patients with previously treated KRASG12C-mutant non-small cell lung cancer, indicating its efficacy in this specific cancer type.

Patients treated with adagrasib had a median overall survival of 11.7 months, and the drug was effective in reducing brain metastases in 33% of patients with such conditions, highlighting its potential for managing advanced disease.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adagrasib Response Remains Strong in NSCLC. [2022]

Adagrasib demonstrates durable efficacy in patients with advanced KRASG12C non-small cell lung cancer, with about one in three patients surviving after 2 years of treatment.

The long-term safety profile of adagrasib remains manageable, as no new toxicities were reported during the study, indicating it is a safe option for previously treated patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adagrasib's Efficacy Sustained in KRASG12C NSCLC. [2023]

Sotorasib is a first-in-class oral medication that specifically targets the KRAS G12C mutation in non-small cell lung cancer (NSCLC), showing a clinically relevant objective response rate in patients during the CodeBreaK 100 trial.

The drug has a manageable safety profile, allowing for dose adjustments to handle any side effects, making it a valuable treatment option for patients with advanced KRAS G12C mutation-positive NSCLC who have already undergone other therapies.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. Lee, A.[2022]

References

1. United States pubmed.ncbi.nlm.nih.gov

Targeted Therapies for Previously "Undruggable" KRAS-Mutated Non-Small Cell Lung Cancer: A Review of Sotorasib and Adagrasib. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Another KRAS Inhibitor Holds Its Own. [2021]

3. England pubmed.ncbi.nlm.nih.gov

An evaluation of sotorasib for the treatment of patients with non-small cell lung cancer with KRASG12C mutations. [2022]

4. United States pubmed.ncbi.nlm.nih.gov

Sotorasib Tackles KRASG12C-Mutated Pancreatic Cancer. [2022]

5. United States pubmed.ncbi.nlm.nih.gov

Frontline Promise for Adagrasib-Pembrolizumab Combination. [2023]

6. United States pubmed.ncbi.nlm.nih.gov

FDA Approval Summary: Sotorasib for KRAS G12C-Mutated Metastatic NSCLC. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Adagrasib Response Remains Strong in NSCLC. [2022]

8. United States pubmed.ncbi.nlm.nih.gov

Adagrasib's Efficacy Sustained in KRASG12C NSCLC. [2023]

9. France pubmed.ncbi.nlm.nih.gov

Sotorasib: A Review in KRAS G12C Mutation-Positive Non-small Cell Lung Cancer. [2022]